Flavopiridol in Treating Patients With B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma - Full Text View

Sponsors and Collaborators:	Arthur G. James Cancer Hospital & Richard J. Solove Research Institute National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00377104

Purpose

RATIONALE: Drugs used in chemotherapy, such as flavopiridol, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase I trial is studying the side effects and best dose of flavopiridol in treating patients with B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma.

Condition	Intervention	Phase
Leukemia Lymphoma	Drug: alvocidib Procedure: cytogenetic analysis Procedure: immunoenzyme technique Procedure: immunologic technique Procedure: laboratory biomarker analysis Procedure: mutation analysis Procedure: pharmacological study Procedure: polymorphism analysis Procedure: protein expression analysis	Phase I

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Lymphoma

Drug Information available for: Alvocidib Flavopiridol

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Phase I Dose-Escalation Study of Flavopiridol (NSC 649890) Administered as a 30 Minute Loading Dose Followed by a 4-Hour Infusion in Patients With B-Cell Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) Following Cytoreduction With Chemotherapy

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Toxicity profile [ Designated as safety issue: Yes ]
Dose-limiting toxicity [ Designated as safety issue: Yes ]
Maximum tolerated dose [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Pharmacokinetics and cellular pharmacodynamics [ Designated as safety issue: No ]
Complete response (CR) and overall response rate (CR and partial response) [ Designated as safety issue: No ]

Estimated Enrollment:	24
Study Start Date:	September 2006
Estimated Primary Completion Date:	September 2007 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Determine the toxicity profile, dose-limiting toxicity, and maximum tolerated dose of flavopiridol as consolidation chemotherapy after cytoreduction chemotherapy in patients with B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma.

Secondary

Determine the pharmacokinetics and cellular pharmacodynamics of flavopiridol in these patients.
Determine the complete response (CR) and overall response rate (CR and partial response) of patients treated with flavopiridol.

OUTLINE: This is a dose-escalation study.

Patients receive flavopiridol IV over 30 minutes (loading dose), followed by flavopiridol IV over 4 hours on days 1, 8, and 15. Treatment repeats every 5 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. A total of 12 patients are treated at the MTD (i.e., recommended phase II dose).

Patients undergo blood collection at baseline and periodically during study for pharmacokinetic and cytokine studies (levels of tumor necrosis factor-alpha, interleukin [IL]-6, -11, and -16) by enzyme-linked immunosorbent assay (ELISA). Interphase cytogenetics, p53 mutational status, p53/ATM function, V_H mutational status, zeta-chain-associated protein kinase 70 (ZAP-70) overexpression, and single nucleotide polymorphisms are also examined.

After completion of study treatment, patients are followed at 2 months and then every 3 months for 5 years.

PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of 1 of the following:
- B-cell chronic lymphocytic leukemia (CLL)
- Small lymphocytic lymphoma (SLL)
Must have received 1-3 prior therapies for CLL
- Completed therapy 2-12 months ago
- Prior therapy must have led to a partial response or greater
- No evidence of progressive disease

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Absolute neutrophil count ≥ 1,000/mm³
WBC ≤ 5,000/mm³
Platelet count ≥ 50,000/mm³
Cytopenia allowed
Creatinine < 2.0 mg/dL
Bilirubin ≤ 1.5 times normal (unless due to Gilbert's disease or hemolysis)
AST ≤ 2 times normal (unless due to hemolysis)
No secondary malignancy or other disease that would limit survival to < 2 years
No history of inflammatory bowel disease unless inactive for > 2 years
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No other concurrent chemotherapy
No concurrent radiotherapy
No concurrent dexamethasone or other corticosteroid-based antiemetics
No concurrent chronic corticosteroid therapy
No other concurrent hormonal therapy except for the following:
- Steroids for new adrenal failure
- Hormones for nondisease-related conditions (e.g., insulin for diabetes)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00377104

Locations

United States, Ohio
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center	Recruiting
Columbus, Ohio, United States, 43210-1240
Contact: Clinical Trials Office - OSU Comprehensive Cancer Center 614-293-4976 osu@emergingmed.com

Sponsors and Collaborators

Arthur G. James Cancer Hospital & Richard J. Solove Research Institute

National Cancer Institute (NCI)

Investigators

Study Chair:

John C. Byrd, MD

Arthur G. James Cancer Hospital & Richard J. Solove Research Institute

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications of Results:

Byrd JC, Lin TS, Dalton JT, Wu D, Phelps MA, Fischer B, Moran M, Blum KA, Rovin B, Brooker-McEldowney M, Broering S, Schaaf LJ, Johnson AJ, Lucas DM, Heerema NA, Lozanski G, Young DC, Suarez JR, Colevas AD, Grever MR. Flavopiridol administered using a pharmacologically derived schedule is associated with marked clinical efficacy in refractory, genetically high-risk chronic lymphocytic leukemia. Blood. 2007 Jan 15;109(2):399-404. Epub 2006 Sep 26.

Phelps MA, Wu D, Dai Z, et al.: Population pharmacokinetics, pharmacodynamics and pharmacogenomics of flavopiridol with a clinically active dosing schedule in patients with chronic lymphocytic leukemia. [Abstract] American Association for Cancer Research: 98th Annual Meeting, April 14-18, 2007, Los Angeles, CA. A-928, 2007.

Study ID Numbers:	CDR0000501975, OSU-05116, OSU-IRB-2006C0031
Study First Received:	September 13, 2006
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00377104
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

B-cell chronic lymphocytic leukemia
stage I chronic lymphocytic leukemia
stage II chronic lymphocytic leukemia
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia

contiguous stage II small lymphocytic lymphoma
noncontiguous stage II small lymphocytic lymphoma
stage I small lymphocytic lymphoma
stage III small lymphocytic lymphoma
stage IV small lymphocytic lymphoma

Study placed in the following topic categories:

Chronic lymphocytic leukemia
Flavopiridol
Lymphatic Diseases
Leukemia
Leukemia, Lymphoid
Immunoproliferative Disorders

Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, B-cell, chronic
Lymphoproliferative Disorders
Leukemia, B-Cell
Lymphoma

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Antineoplastic Agents
Therapeutic Uses

Growth Substances
Physiological Effects of Drugs
Enzyme Inhibitors
Growth Inhibitors
Protein Kinase Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 15, 2009